A-80915A

The microbial production, isolation, and structure elucidation of four new napyradiomycin congeners (1-4) is reported. The structures of these compounds, which are new additions to the marine-derived meroterpenoids, were defined by comprehensive spectroscopic analysis and by X-ray crystallography. Using fluorescence-activated cell sorting (FACS) analysis, napyradiomycins 1-4 were observed to induce apoptosis in the colon adenocarcinoma cell line HCT-116, indicating the possibility of a specific biochemical target for this class of cytotoxins.

As part of our continuing interest in exploring the chemistry of actinomycete bacteria uniquely adapted for survival in ocean sediments, we encountered several new strains, which by 16S rDNA sequence-based phylogenetic analysis were recognized as members of a new genus (tentatively called MAR4) within the family Streptomycetaceae. We report here the isolation and structure elucidation of three new chlorinated dihydroquinones (1-3) and one previously reported analogue, 4, from our strain CNQ-525, isolated from ocean sediments collected at a depth of 152 m near La Jolla, California. The compounds formally possess new carbon skeletons, but are related to several previously reported metabolites of the napyradiomycin class. The structures of the new molecules, which possess significant antibiotic properties and cancer cell cytotoxicities, were assigned by comprehensive spectral measurements and by comparison with NMR and other spectral data from the antibiotic A80915C (5), the full stereostructure of which was recently assigned by X-ray diffraction methods.